不同骨转移潜能人前列腺癌细胞亚株的筛选

Selection of human prostate carcinoma subpopulations with different metastatic potential to bone

背景与目的:前列腺癌具有很高的骨转移率,是导致患者死亡的主要原因,但是其机制仍不清楚。利用裸鼠肿瘤转移模型筛选人前列腺癌不同骨转移潜能的细胞亚株,通过分析其细胞生物学特性,将为今后探索前列腺癌骨转移机制提供模型。方法:采用人前列腺癌细胞系PC-3左心室注射法制作裸鼠肿瘤转移模型,分别获取骨和淋巴结转移灶内的肿瘤细胞,经体外培养及造模,筛选高、低骨转移潜能的细胞亚株。结果:筛选出具有高、低骨转移潜能的细胞亚株T3B和P24,其裸鼠体内骨转移率分别为8/10(80%)、1/10(10%),与母系PC-3细胞6/15(40%)比较差异有显著性(P<0.05);细胞生物学特性分析显示T3B、P24和PC-3的体外黏附率分别为112%±8%、80.3%±2.7%和77%±4%,侵袭能力分别为53±6个/视野、31±3个/视野和24±5个/视野,T3B的细胞黏附和侵袭能力均显著高于P24和PC-3(P<0.01),三者体外细胞增殖率、软琼脂克隆形成率、裸鼠皮下成瘤率及瘤体大小的差异无显著性(P>0.05)。结论:运用裸鼠肿瘤转移模型反复筛选,获得高(T3B)、低(P24)骨转移潜能的人前列腺癌PC-3细胞系亚株。

Background and purpose： Bone is the most common site of metastasis in prostate cancer and is the main cause of death for patients with prostate cancer. The molecular mechanisms of prostate cancer cells that easily metastasize to bone remain unknown. To investigate the process, the purpose of this study is to screen cell substrains with different metastatic potential to bone from human prostate carcinoma cell line that that has been implanted in nude mice. Animal models of bone metastases of prostate cancer could be established, biological characteristics of the cell. substrain could be further detected. Methods： Human prostate carcinoma cell line PC-3 was injected into the left cardiac ventricle of nude mice to generate metastases in vivo, then PC-3 cell subpopulations were screened out by serial recovery from bone or lymph node metastasis and inoculation in vitro. Results： The subpopulations of PC-3 with different bone metastasic potential were obtained by selection in vivo and denominated as T3B and P24. Compared to P24（ 1/10, 10%） and parental PC-3（6/15, 40%）, TsB showed a higher metastatic potential to bone（ 8/10, 80%） in vivo, and presented significant increase in the adhesion and invasion ability in vitro study （P 〈 0.01）, but no significant difference from the cells in terms of soft-agar colony formation rate, tumorigenicity and tumor growth rate（ P 〉 0.05）. Conclusions： Human prostate carcinoma cell substrains with different metastatic potential to bone were obtained in nude mice.